Schistosomiasis which afflicts over 200 million people in 76 countries is a major cause of morbidity in the world. Safe and effective drugs such as praziquantel are available for the treatment of uncomplicated schistosomiasis. They provide interim control of disease. However, the challenge today is not so much in the clinical management of individual patients but rather in the control of transmission and reduction of morbidity in endemic populations. A long-term approach to schistosomiasis control is a vaccination program that would result in reduced transmission and reduced morbidity. The major goal of this research is to improve the efficacy of identified schistosome vaccine candidates and demonstrate their efficacy in baboons as a prelude to human clinical trials. Our previous research has demonstrated that antioxidant enzymes (superoxide dismutase and glutathione peroxidase) can induced via DNA vaccination greater than 40% protection against challenge infection. We have also demonstrated that CT-SOD as a DNA vaccine is able to engender a response that eliminates adult worms and thus may have therapeutic as well as prophylactic value as a vaccine. In addition, we have demonstrated that a fragment of the schistosome filamin gene is able to confer significant levels of protection. We hypothesize that filamin targets both the larval and adult stages of S. mansoni. We propose to improve the vaccine strategy to maximize the protective immune response and to define T and B cell epitopes for inclusion in a subunit vaccine. The ultimate goal of the proposed research is to develop an efficacious vaccine that contains parasite-specific epitopes for human clinical trials.